Abstract & Commentary
Synopsis: Survival benefits in the first year after acute MI, in patients 65 years or older, seem to differ according to specific ACE I prescribed.
Source: Pilote L, et al. Ann Intern Med. 2004;141:102-112.
Ramipril was associated with lower mortality than most other angiotensin converting enzyme inhibitors (ACE I) in elderly patients after acute myocardial infarction (MI). Several randomized, controlled trials show that ACE I improve survival in patients who have an acute MI. However, existing data from trials do not address whether all ACE I benefit patients similarly.
The object of this study was to evaluate whether all ACE I are associated with similar mortality in patients 65 years of age or older who have had an acute MI. This was a retrospective study that used linked hospital discharge and prescription databases containing information on 18,453 patients 65 years or older, who were admitted for an acute MI between April 1996 and March 2000. The source of the patients population was 109 hospitals in Quebec, Canada. In the study, 7512 patients satisfied the criteria, filling a prescription for ACE I within 30 days of discharge, and continued to receive the same drug for at least 1 year.
The association between specific drugs and clinical outcomes was measured by using Cox proportional hazard models with adjustments for demographics, clinical, physician, and hospital variables and dosage categories, represented by time dependent variables. Pilote and colleagues concluded that survival benefits in the first year after acute MI in patients 65 years or older seem to differ according to specific ACE I prescribed. Ramipril was associated with less mortality than most other ACE I.
Comment by Ralph R. Hall, MD, FACP
Pilote et al, as well as Hennessey and colleagues,1 note a number of limitations of this study. The lack of detailed clinical information regarding the database used, for instance, what other medications were administered while the patients were hospitalized, etc. are not available to evaluate.
It was puzzling that perindopril was not included with ramipril in Pilote et al’s conclusions. The mortality rate in the perindopril treated group was not statistically different from patients treated with ramipril.
It is also important that the ramipril and perindopril patients had the greatest percentage of their care provided by a cardiologist, and that in both of these groups, 70% of the patients received beta blockers, while only 45% of the group receiving captopril (the group with the highest mortality) received beta blockers. The lisinopril group had the lowest mortality of the other ACE I studied, and had the highest rate of beta blocker administration within these groups. One could therefore make a strong case that the outcomes in this study were due to the inclusion of beta blocker treatment. Pilote et al state that they adjusted for this variable, but the data are not available to verify this statement.
Hennessy et al1, in their editorial, also point out that the use of beta blockers was associated with better results. They suggest that this may indicate better care in these groups, or that a higher percentage of these patients had fewer contra indications for beta blockers, and therefore, may have been less sick. Further, when they compare this study with the criteria suggested by McAlister et al2 for evaluating non-randomized studies of drug class effect, this study of ACE I would be hypothesis generating rather than be used for clinical action.
So which ACE I should we use? At this time a reasonable approach would be based on dosing frequency, cost, and the clinician’s familiarity with the agent used. In addition, one should make sure that additional therapy such as diet, beta blockers, and statins be used appropriately.
Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
1. Hennessy S, et al. Ann Intern Med. 2004;141: 157-158.
2. McAlister FA, et al. JAMA. 1999;282:1371-1377.